Transcript Leadership Kansas Presentation 7-07

Drug Discovery, Delivery
and Development
at the University of Kansas
Bringing Pharmaceutical Industry Best
Practices to an Academic Setting
Scott Weir, PharmD, PhD
Office of Therapeutics, Discovery and Development
University of Kansas Cancer Center
Our Work Is Imperative
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Cancer is the #1 killer under the age of 85
12,760 will be diagnosed with cancer in 2007
5,290 will die from cancer in 2007
Kansas’ cancer rates are falling at less than 1/3 of the
national average
» In 2007, cancer rate in Kansas (-0.6) was half national
average (-2.1)
American Cancer Society. Statistics for 2007.
Our Work Is Imperative
• Underserved Region
» National Cancer Program
• Closest NCI Comprehensive Cancer Center is at least
250 miles away
NCI Designated Centers
• Statewide Access Problem
» Limited access to
cutting-edge
clinical trials in
rural populations
Cancer Center (24)
Comprehensive Cancer Center (39)
Planning Grant (6)
NCI Progress
NCI Designation Differentiators
Drug Discovery &
Development
Office of
Therapeutics
Discovery &
Development
Community-based
Approach
Clinical
Trials
Office
Results
More advanced cancer prevention,
early detection, treatment, and survivorship
Drug Discovery, Delivery & Development
Why are we in this risky business?
• Patients
• Conduct research which leads to improved disease treatment,
prevention and control therapies
• Support efforts to establish an NCI designated Comprehensive
Cancer Center
• Support regional clinical and translational research efforts, i.e.,
Heartland Institute for Clinical and Translational Research
• University
• Increase overall research funding
• Trains the next generation of drug discovery and development
scientists
• Create commercial opportunities for the University
• Region
• Contributes to life sciences and economic growth
The Vision
Drug Discovery, Delivery and Development
• Establish KU as the number one academic institution in
advancing anti-cancer agents from discovery to patients
• Establish a University-wide, fully integrated organization
• Be recognized as a top academic institution in the
commercialization of pharmaceutical intellectual property
KUCC Model
Basic, Drug
Discovery &
Translational
Research
Drug
Development
& Clinical
Research
NCI Designation Pathway
World-class
Cancer Care
Education &
Outreach
2016
Vision
The Strategy
Drug Discovery, Delivery and Development
• Balanced drug pipeline
» Focus on novel therapies and targets
» Improved delivery of marketed drugs
• Alignment with KU Translational Research priorities
» NCI designation of University of Kansas Cancer Center
» Heartland Institute for Clinical and Translational Research
• Leverage internal and external (outsourcing) expertise
• Bring pharmaceutical industry best practices to KU
» High performance project teams
» “Pharma” drug profiling
• Partnering with industry and other academic institutions
Drug Discovery, Delivery & Development
KU Strengths
• #4 School of Pharmacy (based on total NIH funding, #1
based on NIH funding per faculty FTE)
• Established KU cores and centers
• University priority and commitment
• Stowers Institute for Medical Research
• Ewing Kauffman Foundation
• Wealth of drug development resources in the region
• Life sciences growth in the region
• Focus on collaboration with academic, non-profit and
industry partners
Drug Discovery, Delivery & Development
Management Oversight of the Program
Scott J. Weir, PharmD, PhD
• Director, Office of Therapeutics Discovery &
Development
• 20 years at Marion Laboratories, MMD, HMR, Aventis,
Quintiles and Aptuit
• Expertise in advancing compounds from discovery to
clinical proof of concept
• Management of drug discovery, delivery and
development
G. Sitta Sittampalam, PhD
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Deputy Director, Office of Therapeutics, Discovery and
Development
23 years at Eli Lilly & Company
High throughput screening and lead optimization
expertise
Oversight of biology and chemistry interface
Drug Discovery, Delivery & Development
Drug Discovery, Delivery & Development
Reengineered Drug Discovery Process
Target -> Chemical Hit
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Target
Selection
&
Validation
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Target
Production
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4
High
Chemical
Throughput
Hit
Screening Identification
Chemical Hit -> Lead
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Define Lead Prediction of In vitro
Selection
PhysioPotency &
Criteria
Chemical Selectivity
Properties
In vivo
Proof
of Concept
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Early
ADMET
Lead ->
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Pre –
In vivo and Prepare for
Formulation
In vitro
IND
Screening
ADMET
Enabling
Profiling
Activities
Enabling Processes
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Project prioritization
Project management
Compound management
Process chemistry
Communications
F.
G.
H.
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J.
Development
Candidate
Information technology
Chemoinformatics
Bioinformatics
Regulatory strategy
IP management
Drug Discovery, Delivery & Development
Drug Discovery Leadership
Barbara N. Timmermann, PhD
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Chair, Department of Medicinal Chemistry and
University Distinguished Professor
27 years experience in natural products chemistry
Principal Investigator, Center for Cancer Experimental
Therapeutics
Leadership role in reengineering KU Drug Discovery
Jeffrey Aube', PhD
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Professor of Medicinal Chemistry
Director, Chemical Methodology and Library Design
Center of Excellence
24 years experience in medicinal chemistry
Directing chemistry support laboratory for KU Drug
Discovery program
Drug Discovery, Delivery & Development
Drug Discovery Leadership
G. Sitta Sittampalam, PhD
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Deputy Director, Office of Therapeutics, Discovery and
Development
23 years at Eli Lilly & Company
High throughput screening and lead optimization
expertise
Oversight of biology and chemistry interface
Rathnam Chaguturu, PhD
• Director, High Throughput Screening Lab
• 24 years industry experience in drug discovery at
FMC Corporation and Sierra Biosciences
• Pioneer of high throughput screening technology
Drug Discovery, Delivery & Development
Drug Delivery Center
• Planning grant from Kansas Bioscience Authority to establish worldclass innovation center
• Builds on KU’s strong history in drug delivery
• Managed as an industry unit by pharma experts
• Collaborations with
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Universities
Industry
Venture Capital
Federal Funding Sources
State Economic Development Organizations
Foundations and Societies
• Current plan to grow drug delivery research and service work from
currently ~$4.5M to ~$15M annually
Drug Discovery, Delivery & Development
DDC Large Molecule Core Competencies
1
Pre-formulation /
Characterizations
•Empirical phase diagrams
•Protein dynamics
2
Screening for
stabilizers /
additives
•HTP
•Physical properties
3 Formulation
Development /
Accelerated
Screening
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HTP Physical Screening
(Temperature, PH, Ionic strength (salt),
Protein concentration, Agitation,
Freeze / Thaw, Chemical degradation
(HPLC-MS) )
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Optimization
Physical properties of drug
substance
Drying technologies
A) Biophysical characterization, pre-formulation, and formulation of
macromolecules (Process steps 1 & 3)
Core Competencies
B) Stabilization of macromolecules and their
complexes
C) Solid formulations of biopharmaceuticals
using lyophilization/freeze drying
D) Adjuvant API formulations for vaccine delivery
E) Problem solving - Formulation, delivery and
process development
F) Novel methodologies for macromolecule
characterization
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Real Time Stability
Physical & Biological
Properties
Drug Discovery, Delivery & Development
DDC Small Molecule Core Competencies
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Lead Optimization
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Physical/Chemical
Characterization
• Drugability
» In vitro absorption
» In vitro metabolism
» Protein binding
» Early ADME
• Solubility
• Stability
• Crystalline form
• Phase-solubility
• Polymorphism
• Degradation product profile
• Water binding isotherms
3
Formulation
Development
• Solids
» Immediate release
» Controlled release
» Tablets and beads
• Liquid
» Oral and injectable
» Lyophiles
4
Analytical Methods
Development
5
Preclinical
In-vivo Evaluation
• Stability indicating
» API
» Drug product
• Bioanalytical
» Analyte in blood, plasma
and tissue
» Biomarkers
• Model
» Canine, rodent, primate
• Administration route
» Parenteral
» Non-parenteral
• Pharmacokinetics
» Clearance, bioavailability
A) Formulation of small molecule drugs for preclinical and clinical
studies including solid and liquid dosage forms
Core Competencies
B) Development of novel drug delivery technologies.
C) Problem solving in preclinical drug development.
D) Physical and chemical characterization of drug molecules.
E) Design and synthesis of prodrugs.
F) Development of bioanalytical methods.
G) Rodent and non-rodent pharmacokinetic
and pharmacodynamic studies.
DDET
Drug Delivery Leadership
Valentino Stella, PhD
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Distinguished Professor, Pharmaceutical Chemistry
Principle Investigator, NCI Contract, Development of
Dosage Forms and Delivery Systems for Antitumor Agents
Formulated Taxol®, Velcade®, pentostatin
Pro-drugs
Development of Captisol®
Roger A. Rajewski, PhD
• Director, Biotechnology Innovation and Optimization Center
• 18 years industrial and academic experience
• Pro-drugs
• Development of Captisol®
• Leadership role in reengineering KU Drug Discovery
DDET
Drug Delivery Leadership
Charles (Russ) Middaugh, PhD
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Higuchi Distinguished Professor, Pharmaceutical
Chemistry
Laboratory for Macromolecular and Vaccine Stabilization
Protein folding and stabilization
Formulation and delivery of peptides, proteins, nucleic
acids, viruses and bacteria as pharmaceutical agents
Pharmaceutical industry experience
Drug Discovery, Delivery & Development
Project Management
• High performance project teams
• Led by project managers with
pharma and CRO experience
• Project planning
» Objectives
» Go/no go decision points
» Decision criteria
» Completely integrated with
IP management activities
» Integrated plans including
studies conducted with
industry partners
• Pharma “profiling” aids to best
position IP for licensing
Drug Discovery, Delivery & Development
Project Management
Melinda Broward, BSc, MSc
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Project Director, Office of Therapeutics, Discovery and
Development
19 years pharmaceutical industry experience
Expertise in preclinical drug safety (toxicology and
safety pharmacology), early ADME and high throughput
screening
Michael B. Hughes, BSc, MBA
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Project Director, Office of Therapeutics, Discovery and
Development
14 years pharmaceutical industry experience
Expertise in analytical chemistry, pharmaceutics and
project management
Drug Discovery, Delivery & Development
Collaboration
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Stowers Institute for Medical Research
Kansas Bioscience Authority
Kansas Technology Enterprise Corporation
Children’s Mercy Hospital
OncImmune Inc.
Mayo Clinic Comprehensive Cancer Center
Scripps Research Institute
Beckloff Associates
Cerner Corporation
Universities
Local Start-Up Companies
Contract Drug Development Organizations
Non-profit foundations and societies
Drug Discovery, Delivery & Development
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Drug Discovery, Delivery & Development
Funding Sources
• R&D Infrastructure
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NIH and NCI funded centers and cores
KTEC Biotechnology Innovation and Optimization Center
Kansas Bioscience Authority
KU Endowment
• Federally funded projects
» Reproductive Biology Center of Excellence
» Alzheimer’s Disease
• Partnering
» Supporting existing local companies and future start-ups
» Licensing technology to pharma
» Translational research focused foundations and societies
Drug Discovery, Delivery & Development
Final Messages
• KU Drug Discovery and Development is a cross-campus, multiinstitutional program
• Success is being driven by
» Applying industry best practices to university
» Creating an integrated, efficient drug discovery and development
organization
» Establishing high performance, highly collaborative project teams
through effective planning and management
» Leveraging relationships with other institutions and industry
partners to advance projects and strengthen our program
• KU Drug Discovery and Development plays a key role in establishing
an NCI designated comprehensive cancer center at the University of
Kansas